Synthesis of 6,8,9-tri- and 2,6,8,9-tetrasubstituted purines by a combination of the Suzuki cross-coupling, N-arylation, and direct C-H arylation reactions.
Novel practical methodology of synthesis of a several types of di-, tri-, and tetraarylpurine derivatives by a combination of regioselective Suzuki cross-coupling reactions and/or Cu-catalyzed N-arylation with direct C-H arylations was developed. 6,8-Diaryl- and 2,6,8-triaryl-9-isopropylpurines were prepared by one or two cross-couplings of 6-chloro- or 2,6-dichloro-9-isopropylpurine with arylboronic acids followed by Pd-catalyzed C-H arylation by aryl halides to position 8. 6-Chloropurine and adenine underwent Cu-catalyzed N-arylation to position 9 with boronic acids, followed by cross-coupling with AlMe3 and/or C-H arylation to obtain 8,9-diaryl-6-methylpurines or 8,9-diaryladenines (accompanied by products of partial N-arylation of adenine in position 6). The methodology is suitable for construction of small libraries of modified purines.
Cerna
Igor
I
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, CZ-16610, Prague 6, Czech Republic.
Pohl
Radek
R
Klepetárová
Blanka
B
Hocek
Michal
M
D001632:Bibenzyls / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry
D001632:Bibenzyls; D011687:Purines; D002244:Carbon; C040105:combretastatin; D006859:Hydrogen; D009584:Nitrogen